DOCSLIB.ORG

Fetuin-A: a Novel Link Between Obesity and Related Complications

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Fetuin-A: a Novel Link Between Obesity and Related Complications International Journal of Obesity (2015) 39, 734–741 © 2015 Macmillan Publishers Limited All rights reserved 0307-0565/15 www.nature.com/ijo REVIEW Fetuin-A: a novel link between obesity and related complications JF Trepanowski, J Mey and KA Varady Fetuin-A (FetA) is a 64-kDa glycoprotein that is secreted from both the liver and adipose tissue. Circulating FetA is elevated in obesity and related disorders including type 2 diabetes mellitus, nonalcoholic fatty liver disease and the metabolic syndrome; and a FetA-related parameter, caliciprotein particle, is highly relevant to vascular calcification in overweight/obese patients with chronic kidney disease. FetA level is also associated with impaired insulin sensitivity and glucose tolerance. Accumulating evidence suggests that elevated FetA level causes impaired glycemic control, as FetA has been implicated in impairment of insulin receptor signaling, toll-like receptor 4 activation, macrophage migration and polarization, adipocyte dysfunction, hepatocyte triacylglycerol accumulation and liver inflammation and fibrosis. Weight loss, aerobic exercise, metformin and pioglitazone have each been shown to be effective for reducing FetA level. International Journal of Obesity (2015) 39, 734–741; doi:10.1038/ijo.2014.203 INTRODUCTION relationship, epidemiologic, mechanistic (cell, animal and human Fetuin-A (FetA) is a 64-kDa glycoprotein that is found in relatively models) and interventional research are each summarized. high concentrations in human serum (300–1000 μgml− 1).1–3 Although all relevant research is discussed, special emphasis is Fetuin was first discovered in 1944 in bovine calves, and it given to studies that have been published as the most recent 19,20 derived its name from ‘fetus’ to reflect the observation that fetal reviews of FetA and obesity. serum contained the highest concentration of this protein.4 Fetuin was renamed ‘fetuin-A’ in 2000 upon the discovery of a fetuin-like SEARCH STRATEGY molecule termed ‘fetuin-B’.5 Human FetA is also known as α2- Heremans-Schmid glycoprotein (AHSG);6 this naming honors the A PubMed search was conducted through October 2014 of (independent) discoverers of the human homolog of FetA, publications in English. The following input was used for the Heremans7 along with Bürgi and Schmid.8 search: (FetA or AHSG) and (obesity or diabetes or metabolic In human adults, FetA is mainly expressed and secreted from syndrome or NAFLD or cardiovascular disease (CVD) or kidney the liver and adipose tissue. Epidemiologic research consistently disease or nephropathy or glucose or palmitate or insulin receptor observes elevated circulating FetA in obesity9 and related or inflammation or toll-like receptor 4 or adipocyte or diet or complications, such as type 2 diabetes mellitus (T2DM),1 the exercise or metformin). This search yielded 599 potentially metabolic syndrome10 and nonalcoholic fatty liver disease relevant articles. Additional articles were identified using the (NAFLD).11 Moreover, FetA level is associated with many references listed in these manuscripts. Intervention studies were parameters related to metabolic health, such as insulin considered for review only if they: (1) included a subject sensitivity,3 glucose tolerance,11 circulating lipid levels10 and population that was overweight/obese (body mass index (BMI) ⩾ −2 circulating levels of both pro- and anti-inflammatory proteins.12 25.0 kg m ) and/or presented with T2DM and/or presented FetA also has an important role in calcification inhibition,13 with NAFLD; and (2) examined an intervention that typically particularly in patients with chronic kidney disease (CKD).14 reduces body weight and/or improves insulin sensitivity. Articles Recent research is the uncovering mechanisms that underlie the were selected for inclusion in this review if they provided evidence relationship between FetA and obesity-related complications. for an association between FetA level and obesity or related fi Much of this research can be categorized as explaining either metabolic conditions. A total of 87 articles were nally selected. (1) how glucolipotoxicity induces FetA expression or (2) how FetA promotes metabolic dysfunction. EPIDEMIOLOGIC DATA Intervention trials demonstrate that diet,15 aerobic exercise,16 gastric bypass surgery,9 metformin17 and pioglitazone18 can each Obesity be employed to reduce circulating FetA. Reductions in FetA level Associations between FetA level and obesity-related parameters are often associated with improvements in insulin-related para- are widely reported in the epidemiologic literature. BMI,21 visceral meters and/or circulating adiponectin.15,16 adipose tissue (VAT)1 and leptin concentration22 are each This is the first comprehensive review to exclusively focus on positively associated with FetA concentration. Furthermore, the relationship between FetA and obesity. To expound on this change in FetA level is associated with the change in visceral Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA. Correspondence: JF Trepanowski, Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 West Taylor Street, Room 506F, Chicago, 60612, IL, USA. E-mail: [email protected] Received 19 June 2014; revised 4 October 2014; accepted 2 November 2014; accepted article preview online 3 December 2014; advance online publication, 6 January 2015 Fetuin-A in obesity and related complications JF Trepanowski et al 735 adipose tissue over a 5-year period.23 Circulating FetA is elevated pressure, fasting glucose level, fasting insulin level, the home- in insulin-resistant obesity compared with insulin-sensitive ostasis model of insulin resistance, OGTT-derived 2-h glucose level obesity.24 and OGTT-derived 2-h insulin level.3,11,37,41,42 FetA concentration The relationship between FetA and obesity appears to be has been found to be negatively associated with high-density mediated at least in part by genetics. A variant of the AHSG gene lipoprotein cholesterol level, adiponectin level and insulin that is associated with lower FetA level is more common among sensitivity measured with the euglycemic clamp.3,11 The AHSG normal weight men compared with overweight and obese men.25 gene is located on chromosome 3q27, a region that has been In addition, bi-directional Mendelian randomization shows evi- identified as a metabolic syndrome susceptibility locus.43 dence of a casual association from circulating FetA to BMI, along 26 with no evidence of reverse causality from BMI to FetA. Nonalcoholic fatty liver disease Circulating FetA is elevated in NAFLD (even when patients with Type 2 diabetes mellitus the same glycemic status are compared),11 and is positively Incident diabetes risk increases in individuals with higher FetA associated with liver fat.3 FetA concentration is also positively concentrations even after adjustment for potential mediators, associated with the rs738409 I148M variant of patatin-like including: body weight, BMI, waist circumference, blood pressure, phospholipase domain-containing 3,44 which is the major blood lipid levels, race, fasting glucose level, HbA1C level, determinant of liver fat content in the general population. C-reactive protein level, adipocytokine levels and liver enzyme A positive association between FetA level and the liver fibrosis levels.1,2,27 A recent investigation found that a positive association score index has been observed.45 However, other studies between FetA concentration and incident diabetes risk existed have reported no association between FetA level and liver only in female participants.21 However, previous research found histology.17,44,46 A negative association between FetA concentra- that this association applied similarly to both genders.1,2,28 tion and the calculated NAFLD fibrosis score was also reported,47 Gestational diabetes patients have elevated FetA level compared although this calculation does not involve measurements derived with healthy pregnant women and non-pregnant controls.29 from liver biopsy or liver imaging. Among NAFLD patients, FetA Moreover, FetA concentration is positively associated with both level has been reported to be positively associated with carotid fasting C-peptide concentration and C-peptide/blood glucose artery intima-media thickness in one investigation,46 and ratio in both gestational diabetes patients and healthy pregnant negatively associated in another.47 Differences in NAFLD diagnosis women.29 Isolated impaired glucose tolerance, but not isolated methodology (liver biopsy for the study reporting a positive impaired fasting glucose, is associated with higher FetA concen- association, abdominal ultrasonography for the study reporting a tration when compared with normal glucose tolerance.11 The negative association) may explain these discrepant findings. reason for this is currently unclear but may be related to the greater degree of peripheral insulin resistance that is typically Chronic kidney disease observed in isolated impaired glucose tolerance.30 In individuals Vascular calcification is a prominent feature of CKD and an with impaired glucose tolerance, but not normal glucose established risk factor for cardiovascular events and cardiovascular tolerance, FetA concentration is negatively associated with insulin mortality.48 FetA is a potent extraosseous calcification inhibitor,13 secretion during an oral glucose tolerance test (OGTT).31 and in studies examining CKD patients (typically with a mean BMI AHSG gene single-nucleotide polymorphisms have been
Load more

Recommended publications
  • Fetuin (␣2-HS-Glycoprotein) Opsonizes Cationic Macrophage- Deactivating Molecules (CNI-1493͞P38 Mitogen-Activated Protein Kinase)
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 14429–14434, November 1998 Medical Sciences Fetuin (a2-HS-glycoprotein) opsonizes cationic macrophage- deactivating molecules (CNI-1493yp38 mitogen-activated protein kinase) HAICHAO WANG*†‡,MINGHUANG ZHANG†,MARINA BIANCHI†,BARBARA SHERRY†,ANDREW SAMA*, AND KEVIN J. TRACEY†§ Departments of *Emergency Medicine and §Surgery, North Shore University Hospital-New York University School of Medicine, and †The Picower Institute for Medical Research, Manhasset, NY 11030 Communicated by George J. Todaro, University of Washington, Seattle, WA, September 22, 1998 (received for review February 5, 1998) ABSTRACT Macrophages become activated by bacterial of circulating fetuin, but it also is expressed by mono- endotoxin (lipopolysaccharide) and other stimuli to release cyteymacrophages (26). The fetuin promoter region has several proinflammatory cytokines and NO. To prevent release of toxic potential interleukin 6-responsive elements (27), and its synthesis or potentially lethal quantities of these factors, the state of is down-regulated during injury and inflammation (20). Fetuin is macrophage activation is counter-regulated by anti-inflamma- an acidic glycoprotein with three N-linked and three O-linked tory mediators (e.g., glucocorticoid hormones, interleukin 10, oligosaccharide chains, whose terminal sugar residues are rich in b and transforming growth factor type ). Fetuin, a negative sialic acid (N-acetylneuraminic acid), contributing to its net acute-phase protein, recently was implicated as an anti- negative charge (28). A role for fetuin as a carrier of bioactive inflammatory mediator, because it is required for macrophage molecules has been proposed based on observations that it binds deactivation by spermine. In the present studies, we found that and carries Ca21 ion (22).
    [Show full text]
  • New Metabolic and Genetic Biomarkers for Diagnosis of Ulcerative Colitis
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 2 August 2021 doi:10.20944/preprints202108.0048.v1 Review New Metabolic and Genetic Biomarkers for Diagnosis of Ulcerative Colitis Elena-Emilia Tudoroiu1, Mihaela-Andreea Costache1 and Maria-Andreea Stancu 1,* and Anca Lucia Pop1 1 Department of Clinical Laboratory, Food Safety, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, Bucharest 020945, Romania, [email protected], [email protected], [email protected], [email protected] * Correspondence: [email protected], (M.S.); [email protected] (A.L.P.) Tel.: +40745009910 Abstract: Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.
    [Show full text]
  • 2HS-Glycoprotein, an Antagonist of Transforming Growth Factor in Vivo
    [CANCER RESEARCH 64, 6402–6409, September 15, 2004] ␣2HS-glycoprotein, an Antagonist of Transforming Growth Factor ␤ In vivo, Inhibits Intestinal Tumor Progression Carol J. Swallow,1,2 Emily A. Partridge,1 Jennifer C. Macmillan,1 Tania Tajirian,1 Gianni M. DiGuglielmo,1 Kazy Hay,1 Melanie Szweras,1 Willi Jahnen-Dechent,3 Jeff L. Wrana,1,2 Mark Redston,1 Steven Gallinger,1,2 and James W. Dennis1,2 1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; 2Departments of Molecular and Medical Genetics and Surgery, University of Toronto, Toronto, Ontario, Canada; and 3Interdisziplina¨ren Zentrums fu¨r Klinische Forschung BIOMAT, Klinikum der Rheinisch-Westfa¨lischen Technischen Hoschschule, Aachen, Aachen, Germany ABSTRACT ␤1-induced epithelial-mesenchymal transition is characterized by down-regulation of E-cadherin expression, loss of tight junctions, and ␤ Transforming growth factor (TGF)- 1 is associated with tumor pro- increased cell motility (1, 10) and is dependent on phosphatidylinosi- gression and resistance to chemotherapy in established cancers, as well as tol 3Ј-kinase/Akt activation (11), a key pathway promoting tumor cell host immune suppression. Here, we show that the serum glycoprotein ␣2-HS-glycoprotein (AHSG) blocks TGF-␤1 binding to cell surface re- invasiveness (12). Epithelial-mesenchymal transition appears to be a ceptors, suppresses TGF-␤ signal transduction, and inhibits TGF-␤- close in vitro correlate of metastatic capacity, and both require coop- induced epithelial-mesenchymal transition, suggesting that AHSG may erative signaling of TGF-␤ and Ras/mitogen-activated protein kinase play a role in tumor progression. In 66 consecutive sporadic human pathways (13, 14). Tumor-derived TGF-␤1 also has paracrine effects colorectal cancer specimens, we observed a 3-fold depletion of ASHG in on host cells that promote angiogenesis, alter matrix turnover, and tumor compared with normal tissue, whereas levels of other abundant suppress immune cell functions (1, 7, 15, 16).
    [Show full text]
  • The Serum Glycoprotein Fetuin-A Promotes Lewis Lung Carcinoma Tumorigenesis Via Adhesive-Dependent and Adhesive-Independent Mechanisms
    Research Article The Serum Glycoprotein Fetuin-A Promotes Lewis Lung Carcinoma Tumorigenesis via Adhesive-Dependent and Adhesive-Independent Mechanisms Madappa N. Kundranda,1 Melodie Henderson,3 Kathy J. Carter,3 Lee Gorden,3 Awadh Binhazim,2 Sanhita Ray,1 Trevor Baptiste,1 Masih Shokrani,1 Maria L. Leite-Browning,3 Willi Jahnen-Dechent,4 Lynn M. Matrisian,3 and Josiah Ochieng1,3 Departments of 1Biochemistry and 2Pathology, Meharry Medical College and 3Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, and 4IZKF BIOMAT, University Clinics, Aachen, Germany Abstract serum concentration drops after trauma, infection, and certain Fetuin-A is a serum glycoprotein in the cystatin family malignancies. Recently, a second protein of the fetuin family called associated with the regulation of soft tissue calcification. We fetuin-B was described in humans and rodents (1). Based on domain tested the role of systemic fetuin in tumor cell growth and homology, overall conservation of cysteine residues and chromo- metastasis by injecting Lewis lung carcinoma (LLC) cells into somal assignments of the corresponding genes in these species, fetuin-B was described as a paralogue of fetuin-A. fetuin-A null and their wild-type (WT) littermate control C57BL/6 mice via the tail vein, s.c., and intrasplenic routes. Fetuin-A has been linked to a number of cellular functions such In the experimental metastasis assay, the lungs of the WT as brain development (2), bone remodeling, and immune function (5, 6). It can also mimic and antagonize the anti-mitogenic effects mice were filled with metastatic nodules, whereas the lungs h of the fetuin-A null mutant mice were virtually free of of transforming growth factor- in test tube assays, in cell culture, colonies at the end of 2 weeks.
    [Show full text]
  • Fetuin a Concentration in the Second Trimester Amniotic Fluid of Fetuses with Trisomy 21 Appears to Be Lower: Phenotypic Considerations
    Hindawi Publishing Corporation Mediators of Inflammation Volume 2012, Article ID 138971, 4 pages doi:10.1155/2012/138971 Research Article Fetuin A Concentration in the Second Trimester Amniotic Fluid of Fetuses with Trisomy 21 Appears to Be Lower: Phenotypic Considerations S. Iliodromiti,1, 2 N. Vrachnis,1 Evangelia Samoli,3 Z. Iliodromiti,1 C. Pangalos,4 N. Drakoulis,5 G. Creatsas,1 and D. Botsis1 1 2nd Department of Obstetrics and Gynecology, University of Athens Medical School, Aretaieion Hospital, 124B Vas. Sofias Avenue, 115 26 Athens, Greece 2 West of Scotland Deanery, Obstetrics and Gynaecology, Glasgow, G3 8BW, UK 3 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, 115 27 Athens, Greece 4 Diagnostic Genetic Centre, 115 28 Athens, Greece 5 Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, 157 71 Athens, Greece Correspondence should be addressed to N. Vrachnis, [email protected] Received 23 July 2011; Revised 21 November 2011; Accepted 21 November 2011 Academic Editor: Teresa Zelante Copyright © 2012 S. Iliodromiti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. Methods. 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit.
    [Show full text]
  • Understanding the Effects of Fetuin-A in Pregnancy
    Central Medical Journal of Obstetrics and Gynecology Editorial *Corresponding author Luis M. Gómez, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee Health Sciences Center, Memphis, TN, USA, Understanding the Effects of Email: [email protected] Submitted: 31 August 2013 Fetuin-A in Pregnancy Accepted: 31 August 2013 Published: 02 September 2013 Luis M. Gómez* Copyright Division of Maternal-Fetal Medicine, University of Tennessee Health Sciences Center, © 2013 Gómez USA OPEN ACCESS Human fetuin-A has emerged as a provocative molecule which actions in pregnancy have become the subject of research Women who present with preeclampsia are at risk of developing especially since the last decade. Also known as alpha-2 Heremans- metabolic syndrome later in their life [13,14]. Initial attempts Schmid glycoprotein, fetuin-A is a circulating glycoprotein to associate fetuin-A with preeclampsia were reported by produced in increased amounts during fetal life by various Shinagawa and Saitoh who found that fetuin-A was more tissues. Similar fetuin-A concentrations in maternal serum and prevalent among urine of women who developed preeclampsia umbilical cord suggest passive placental transfer of fetuin-A [15]; this association persisted after delivery. Park and during pregnancy [1]. The concentration of fetuin-A in plasma colleagues compared maternal serum proteome in women who decreases soon after delivery [2]. In the adult life, it is actively developed severe preeclampsia (n=8) with normal pregnancies secreted into the blood stream mainly by the liver [3]. Research (n=5) [16]; among candidate target proteins, fetuin-A was investigating the effects of fetuin-A in pregnancy has emerged noted to be elevated in severe preeclampsia cases.
    [Show full text]
  • Axial Spondyloarthritis and Inflammatory Bowel Disease
    Rheumatology International Rheumatology https://doi.org/10.1007/s00296-021-04940-1 INTERNATIONAL OBSERVATIONAL RESEARCH Axial spondyloarthritis and infammatory bowel disease: association between disease activity and endothelial dysfunction markers Hanna Przepiera‑Będzak1 · Katarzyna Fischer2 · Marek Brzosko1 Received: 25 May 2021 / Accepted: 28 June 2021 © The Author(s) 2021 Abstract Objective We aimed to assess patients with axial spondyloarthritis (axSpA) and infammatory bowel disease (IBD) for disease activity and serum markers of endothelial dysfunction. Methods We studied 161 patients (123 males, 38 females) with axSpA: 153 with ankylosing spondylitis and 8 with non- radiographic axSpA, and 30 healthy controls (HC). We collected: age; sex; disease duration; extra-articular symptoms (IBD and acute anterior uveitis), comorbidities; human leukocyte antigen B27 status; and treatment. We measured serum inter- leukin (IL)-6, interleukin-18, IL-23, vascular endothelial growth factor (VEGF) epidermal growth factor (EGF), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), and fetuin-A levels. Results IBD was diagnosed in 19 (11.8%) patients with axSpA. Compared to patients with axSpA without IBD, those with IBD had higher serum C-reactive protein (CRP) level (p = 0.05), erythrocyte sedimentation rate (ESR) (p = 0.005), and serum ET-1 levels (p = 0.01). In patients with axSpA and IBD, ET-1 levels correlated positively with CRP level (p = 0.006) and ESR (p = 0.02), and ADMA levels with visual analog scale scores (p = 0.01). Patients with axSpA and IBD had higher serum levels of IL-6 (p = 0.01), IL-18 (p = 0.005), and ADMA (p = 0.01) and lower serum levels of fetuin-A (p = 0.01) than did controls.
    [Show full text]
  • Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects
    life Article Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects Hajnalka L˝orincz 1, Imre Csige 2,3, Mariann Harangi 1, Anita Szentpéteri 1, Ildikó Seres 1, Zoltán Szabó 2, György Paragh 1 and Sándor Somodi 1,2,* 1 Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; [email protected] (H.L.); [email protected] (M.H.); [email protected] (A.S.); [email protected] (I.S.); [email protected] (G.P.) 2 Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; [email protected] (I.C.); [email protected] (Z.S.) 3 Doctoral School of Health Sciences, University of Debrecen, 4032 Debrecen, Hungary * Correspondence: [email protected] Abstract: Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atheroscle- rosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have not been entirely investigated in morbid obese and lean non-diabetic subjects. Methods: One-hundred obese non-diabetic patients (body mass index, BMI: 42.5 ± 8.1 kg/m2) along with 32 gender and age-matched normal weight controls 2 Citation: L˝orincz,H.; Csige, I.; (BMI: 24.5 ± 2.5 kg/m ) were enrolled in our study. Serum fetuin-A and RBP4 were measured by Harangi, M.; Szentpéteri, A.; Seres, I.; ELISA.
    [Show full text]
  • Proteinuria As the Most Relevant Parameter Affecting Fetuin-A Levels in Preeclampsia
    ACTA FACULTATIS MEDICAE NAISSENSIS UDC: 616.61-008.6 DOI: 10.1515/afmnai-2015-0027 Original article Proteinuria as the Most Relevant Parameter Affecting Fetuin-A Levels in Preeclampsia Hussein Kadhem Al-Hakeim, Roaa Ali Muhammed Ali Department of Chemistry, College of Science, University of Kufa, Iraq SUMMARY The present study aimed to examine the factors affecting the possible changes in serum fetuin-A in patients with preeclampsia (PE). The examined factors included the parameters of insulin resistance (IR) [(insulin sensitivity (HOMA%S), insulin resistance (HOMA2IR), and beta-cell functions (HOMA%B)], which were calculated using the HOMA2 calculator, and total and ionized calcium and magnesium levels. Sixty PE patients and thirty healthy pregnant women, which comprised the study group and control group, respectively participated in the present study. Fetuin-A, estradiol, insulin, glucose, total and ionized calcium and magnesium, total protein, albumin, and globulins were measured in their sera. The results of the present study showed that serum total and ionized magnesium and the I.Ca/Mg ratio decreased in PE women. Although the fasting insulin level and HOMA2IR were higher and HOMA2%S was lower in PE compared with the control women, PE did not appear as an overt insulin-resistant state. Serum fetuin-A was low in PE patients compared with the control group because PE women had proteinuria. Fetuin-A levels were not correlated with the characteristics and IR parameters, cations, and estradiol levels, but it was correlated with the severity of proteinuria. These results confirmed the hypothesis that proteinuria results in the loss of fetuin-A because it has a low molecular weight.
    [Show full text]
  • Review FETUIN-A – ALPHA2-HEREMANS
    J Biomed Clin Res Volume 11 Number 1, 2018 DOI: 10.2478/jbcr-2018-0002 Review FETUIN-A – ALPHA2-HEREMANS-SCHMID GLYCOPROTEIN: FROM STRUCTURE TO A NOVEL MARKER OF CHRONIC DISEASES PART 2. FETUIN-A – A MARKER OF INSULIN RESISTANCE AND RE- LATED CHRONIC DISEASES Regina S. Komsa-Penkova, Summary Katya S. Kovacheva1, Georgy M. Golemanov, Fetuin-A is a secretory liver glycoprotein with multiple Veselin P. Penkov2, physiological functions such as regulation of insulin 3 resistance, tissue calci¿ cation, bone metabolism, cellular Zdravka V. Radionova , proteolytic activity, and self-proliferative signaling. Galia B. Georgieva- Fetuin-A is a unique molecule which binds to the insulin Alexandrova, receptor, modulating its sensitivity, and transducing “the Alim V. Izmajlov physiological conditions” (serum levels of the metabolites like glucose, free fatty acids, inÀ ammatory signals) from outside into inside the cells. Plasma fetuin-A levels correlate Division of Biochemistry, with reduced glucose tolerance and insulin resistance. Medical University – Pleven, Impaired insulin sensitivity leads to the development of Bulgaria metabolic syndrome, an increased risk for type 2 diabetes 1Division of Medical Genetics, (T2DM), dyslipidaemias and cardiovascular diseases Medical University – Pleven, (CVDs). Furthermore, fetuin-A inversely correlates with Bulgaria inÀ ammatory and activation biomarkers, e.g. in patients with 2Repromed Medical Centrum – Pleven, T2DM. Thus, circulatory fetuin-A levels may have plausible Bulgaria predictive importance as a biomarker of risk of diabetes and 3Division of Pedagogy and Psychology, negative acute phase protein. Dysregulated, it plays a crucial Medical University – Pleven, role in the pathogenesis of some metabolic disorders and clinical inÀ ammatory conditions like metabolic syndrome, Bulgaria T2DM, CVDs, polycystic ovary syndrome (PCOS), etc.
    [Show full text]
  • Soft Tissue Calcification in Mice Is Governed by Fetuin-A, Pyrophosphate and Magnesium
    bioRxiv preprint doi: https://doi.org/10.1101/577239; this version posted March 14, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Soft tissue calcification in mice is governed by fetuin-A, pyrophosphate and magnesium Anne Babler1*, Carlo Schmitz1*, Andrea Büscher1, Marietta Herrmann1,2, Felix Gremse3, Theo Gorgels4, Jürgen Floege5, Willi Jahnen-Dechent1 1 Helmholtz Institute for Biomedical Engineering, Biointerface Lab, RWTH Aachen University Hospital, Aachen, Germany 2 IZKF Research Group Tissue Regeneration in Musculoskeletal Regeneration, Orthopedic Center for Musculoskeletal Research, University of Würzburg, Würzburg, Germany 3 Helmholtz Institute for Biomedical Engineering, Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen, Germany 4 University Eye Clinic Maastricht, Maastricht University Medical Center, The Netherlands 5 Division of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany *equal contribution Running title: Triple calcification inhibitor deficiency in Fetuin-A-Deficient DBA/2 Mice Corresponding author: Prof. Willi Jahnen-Dechent, Helmholtz Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany, Phone: +49-241-8080163, Fax: +49-241-8082573, E-mail: willi.jahnen@rwth- aachen.de Keywords – calcification, mineral metabolism, fetuin-A, magnesium, pyrophosphate, mouse models Subject Codes - Animal Models of Human Disease, Fibrosis, Inflammation, Proteomics, Peripheral Vascular Disease Word count – XXXX (excl. References and Figure Legends) Total number of figures and tables – X figures, X tables, X supplement figures, X movies 1 bioRxiv preprint doi: https://doi.org/10.1101/577239; this version posted March 14, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • Mammalian Cell Growth Proteins, I. Growth Stimulation by Fetuin* by Theodore T
    MAMMALIAN CELL GROWTH PROTEINS, I. GROWTH STIMULATION BY FETUIN* BY THEODORE T. PUCK,t CHARLES A. WALDREN, AND CAROL JONES: UNIVERSITY OF COLORADO MEDICAL CENTER, DENVER Communicated October 30, 1967 In earlier papers we described the presence and properties of a factor in the fetuin fraction of fetal calf serum which promotes growth of mammalian cells in vitro and enhances their stretching on glass and other surfaces.1 Fetuin is an alpha-globulin, obtained by fractional precipitation with ammonium sulfate, whose major component is a glycoprotein of molecular weight 45,000.1 A synthetic medium was described which when supplemented with both albumin and fetuin produces virtually 100 per cent efficiency of colony growth of single HeLa cells plated in vitro.' Another synthetic medium, F12,2 was later developed in this laboratory which eliminated the need for albumin, greatly reduced the amount of fetuin required for maximal cell growth, and supported slow growth of some but not all cell strains without any protein supplement. Other laboratories have found or confirmed the presence of a growth-stimulating, alpha-globulin serum component,3 but questions have been raised as to whether the active fraction of fetal serum is indeed fetuin, and whether growth-promoting proteins from adult sera are similar to or different from those found in fetal sera.38' 4 The divergences of interpretation which have arisen are due to a variety of causes, including the presence of several components3 in the original fetuin described by Pedersen;6 the ease with which active fetuin preparations can lose their biological activity;" the lack of reliable, quantitative tests for titration of the biological activity of this growth-promoting factor; and the fact that various investigators have used different cells, media, and methodologies for assessment of the biological activities of their fractions.
    [Show full text]